Low-coherence interferometry (LCI) is a well-known optical coherence technique capable of measuring one-dimensional depth-resolved tissue structure with a typical resolution of several microns. Optical Coherence Tomography (OCT) combines LCI with a lateral scanning mechanism to generate cross-sectional images of biological tissues. LCI and OCT are non-invasive imaging techniques, typically using near-infrared light to obtain structural information from human tissues in vivo. The use of OCT for non-invasively imaging ear tissue was taught in U.S. Pat. No. 8,115,934 (hereinafter “Boppart '934,” entitled “Device and Method for Imaging the Ear using Optical Coherence Tomography,” and incorporated herein by reference. Further information regarding the application of OCT to imaging ear tissue may be found in the following references, all of which are incorporated herein by reference:    Xi et al., “High-resolution three-dimensional imaging of biofilm development using optical coherence tomography,” J. Biomed. Opt., vol. 11, pp. 11(3):134001-1-134001-6, (2006).    Pitris et al., “High-resolution imaging of the middle ear with optical coherence tomography: a feasibility study,” Arch. Otolaryngology—Head & Neck Surg., vol. 127, pp. 637-642, (2001).    Jung et al., “Handheld Optical Coherence Tomography Scanner for Primary Care Diagnostics,” IEEE Trans. Biomed. Eng., vol. 58, pp. 741-44, (2011).    Nguyen et al., “Noninvasive in vivo optical detection of biofilm in the human middle ear,” Proc. Nat. Acad. Of Sciences, vol. 109, pp. 9529-34, (May 29, 2012), (“Nguyen 2012”).    Shelton et al., “Optical coherence tomography for advanced screening in the primary care office,” J. Biophotonics, DOI: 10.1002/jbio.0.201200243, (Apr. 18, 2013).
In the prior art, biofilms were imaged in controlled environments, such as within a flow-cell. Two-dimensional and three-dimensional OCT images were shown in Nguyen 2012. Each 2-D image in Nguyen was composed of a series of adjacent 1-D LCI depth scans. Sufficient information exists in the 1-D depth scans to determine the thickness and optical properties of layered structures, such as the layered biofilm on the tympanic membrane.
Various diagnostic applications call, not only for otoscopy in general, but for use of a pneumatic otoscope in particular, for visualizing the ear canal, tympanic membrane, and middle-ear, to detect and diagnose ear diseases such as otitis media (OM) or otitis media with effusion (OME). In pneumatic otoscopy, a special tip is used that effectively seals the ear canal, forming a closed pressure system in the ear. Pneumatic otoscopes are typically equipped with an insufflation bulb connected to the otoscope via a tube, allowing the pressure inside the ear canal to be modulated. These pressure changes cause the thin eardrum to deflect or retract, depending on whether the applied pressure is positive or negative. The amount of deflection gives the physician some indication of the mechanical stiffness of the eardrum. The degree of mechanical stiffness of the eardrum is an indication of whether the eardrum is infected. Additionally, if an effusion (fluid) exists in the middle ear, the eardrum is less mobile than in the case of a healthy ear.
Other than pneumatic otoscopy, there are mainly two in vivo diagnostic methods for identifying middle-ear pathologies. Tympanometry measures sound energy transmission/reflection (i.e., compliance/mobility) of the tympanic membrane by recording a tympanogram in response to air pressure changes inside the ear canal. Tympanograms are classified as type A (normal), type B (indicating middle-ear effusion) or type C (indicating Eustachian tube dysfunction). Acoustic reflectometry measures the acoustic reflectivity spectrum of the middle-ear in response to an incident sound. The curve of the spectrum is used to characterize the extent of OME. Comprehensive evidence assessment on the accuracy (sensitivity and specificity) of the three methods reveals that pneumatic otoscopy has better performance than the two acoustic methods. Moreover, pneumatic otoscopy is more cost-effective and easier to use. Thus, the 2004 clinical practice guideline on OME from the American Academy of Pediatrics has recommended that clinicians use pneumatic otoscopy as the primary diagnostic method. In this respect, all efforts to improve the validity and reliability of pneumatic otoscopy are warranted.
Otoscopy based on pneumatic otoscopes is currently the primary diagnostic tool for various ear pathologies. However, the diagnostic process is currently more subjective than objective, more of an art than a science. One of the biggest problems with current pneumatic otoscopes is that they require a lot of user experience to be effective. Studies have shown that less than half of pneumatic otoscope exams are correctly diagnosed, largely because the measurement is so subjective. Physicians must estimate how mobile the eardrum is by looking at a two-dimensional (2D) image in a plane perpendicular to the axis of motion. Trained eyes are required to decipher a wide variety of tympanic membrane and middle-ear images, some of which are empirically linked to various disease states. Treatments that follow such subjective diagnosis rely on the individual judgments of physicians. Currently, few objective tests are available to assess the significance of disease, and limitations are more evident in the primary care or general pediatrician's office, remote from access to specialists in otolaryngology.
Furthermore, evaluation and monitoring of treatments (such as antibiotic treatments in OM or OME) in patients is often difficult, because quantitative measures are lacking. All these limitations can be ultimately attributed to the qualitative nature of the information acquired, and flow from the fact that a prior art pneumatic otoscope is basically a low-magnification microscopy-type of instrument.
A prior art LCI/OCT otoscope is shown schematically in FIG. 1A, which appears as FIG. 10 in the Boppart '934 patent. As described there, a device 400 for imaging the ear using optical coherence tomography is provided which includes a core imaging unit 410 in communication with a core software unit 430. Preferably, the core imaging unit 410 is not only in communication with, but also integrated within, the device 400 so as to provide a compact portable instrument which allows straightforward clinical operation in an office-based setting. The core imaging unit 410 is in communication with the core software unit 430, as shown in FIG. 1B. If the core imaging unit 410 is integrated within the device 400, then the core software unit can communicate directly with the device 400.
The device 400 can image visible structures (i.e. structures that can be seen with the naked eye) such, as the tympanic membrane, with enough accuracy to account for slight variations or movement in those structures. For example, device 400 can image variations or movement of the tympanic membrane. Additionally, the device 400 can image structures which are not visible to the naked eye, such as middle ear structures behind the tympanic membrane in order to search for tissue, such as biofilms.
In accordance with the operation of LCI or OCT devices, light emitted by a low-coherence source 402 is incident upon ear tissue via otoscope 401, and is combined with a reference beam, such as derived via reference mirror 424, in interferometer 408, thereby gating a detection signal to a tightly localized scattering window. The reference beam may share a common path with the signal beam and be reflected, for example, from a window in the signal beam path. Low-coherence source 402 may be swept in wavelength, and the interferometer output may be wavelength-resolved by spectrometer 412.
The device 400 includes any imaging device which can non-invasively image the middle ear, direct and receive light from the middle ear and send the received light to the core imaging unit 410. Preferably, the imaging device 400 also includes any device which can form a direct line of sight from the tympanic membrane to the outside of the ear, such as an ear speculum. The imaging device 400 includes things such as an otoscope 401, a pneumatic otoscope, ear plugs, ear speculums, and other such devices. In one embodiment, the otoscope 401 is a pneumatic otoscope, such as the MacroView™ otoscope manufactured by Welch Allyn Inc. of Skaneateles Falls, N.Y., or the BETA 200 otoscope manufactured by HEINE Optotechnik of Germany.
Preferably, the imaging device 400 is adapted for selecting and analyzing tissue in the patient's middle ear. This means that the device is capable of non-invasively imaging inside the patient's ear canal and more specifically, non-invasively imaging the patient's middle ear. Preferably, at least a portion of the device is adapted for insertion into the patient's ear canal, allowing for non-invasive imaging of the patient's ear canal and or middle ear. In one embodiment, at least a portion of the device 400 has a diameter or width which does not exceed 1 cm and preferably does not exceed 0.5 cm, so that the device 400 can be inserted into an ear. However, since animal ears can be much larger than human ears, at least a portion of device 400 can be adapted for insertion into those ears and made much larger so as to fit within the ear canal of any animal, large or small.
In one embodiment, the device 400 includes a fiber based device 406 connected with or integrated with the otoscope 401, as shown in FIG. 1B. The fiber based device 406 includes any device which can act as a light guide and carry beams of light from one place to another. Preferably, the fiber based device 406 includes a fiber optic cable. When the otoscope 401 is placed near or within a patient's ear canal 442, light from the inner or middle-ear 444 carried through the fiber based device 406 to the core imaging unit 410. The fiber based device 406 is connected with the otoscope 401. In one embodiment, the fiber based device 406 delivers light into the optical system of the otoscope 401, and uses the existing or modified optics of the otoscope 401 to also direct a near-infrared beam to the middle-ear.
In one embodiment, the fiber based device is attached to an outside surface of the otoscope 401. In one embodiment, the fiber based device 406 is run through at least a portion of the otoscope 401, as shown in FIG. 1B. Preferably, the fiber based device 406 is run through at least portions of the head unit 402 and the ear speculum 404 (otherwise referred to herein as a tip of the otoscope 401). More preferably, the fiber based device 406 is run through the ear speculum 404 and positioned to receive light which enters the ear speculum 404. The ear speculum 404 provides mechanical support for the fiber based device 406 to perpendicularly approach an eardrum 446 to within about 5 mm, enabling non-invasive in-vivo ear diagnosis simultaneously with a regular otoscope exam.
The fiber based device 406 is preferably miniaturized to avoid blocking the field of the view of the otoscope 401, which is approximately 2.5 mm in diameter in some cases. Additionally, it is preferable that the fiber based device 406 be flexible enough to adapt to the curved shape of the ear speculum 404. Because of the dual role played by the fiber based device 406 as an optical source and receiver, the fiber based device 406 should produce a collimated beam or a weakly focused beam with a focus approximately the distance D between a tip 411 of the ear speculum 404 and the eardrum (˜3-5 mm). A divergent beam will deteriorate the collection efficiency of the back-reflected optical signal. These requirements are achieved by fusion-splicing a gradient index (GRIN) fiber (which acts as a focusing element) onto the end of a single mode fiber (SMF) connected to the sample arm of the LCI interferometer. The GRIN fiber lens face is then polished to attain the appropriate angle and total GRIN fiber length.
In one embodiment, the device 400 is configured with a miniature video camera 409, and real-time video of the ear canal and/or eardrum 446 from the device 400 is used to do a wide-field survey, as well as to select or track the location in the ear on the eardrum where an OCT measurement is acquired. The video camera 409 is preferably connected with the ear speculum 404.
In one embodiment, the fiber based device 406 includes a fiber-optic OCT probe which can be used to generate OCT signals, LCI signals, or both OCT and LCI signals. In one embodiment, the location in the inner or middle-ear 444 on an eardrum 446 where an OCT signal is acquired by the device 400 is illuminated, preferably by guiding light through the fiber based device 406 and onto the eardrum 446 in order to collect an OCT signal. The illumination is a low-power (1 mW) NIR beam which does not affect the regular operations of the otoscope 401. The back-reflected NIR beam from the middle-ear tissues is collected by the same fiber based device 406 and used to infer the depth-resolved structures of tissue within the ear 438, and specifically tissue within the inner or middle-ear 444.
In one embodiment, in order to obtain OCT data, more than one OCT signal is acquired. The OCT signals are acquired at high speeds (>250 Hz). This enables rapid collection of large depth-resolved datasets for analysis, as well as tracking of the movement of middle-ear structures (e.g., the eardrum) due to pneumatic operation of the otoscope 401, which can be monitored in real time. The simultaneous capture of a video image of the NIR beam on the eardrum, along with the depth-resolved OCT signals, enables correlation of suspect visual findings with depth-resolved measurements and the generation of OCT data.
In one embodiment, in order to obtain OCT data, an LCI signal is generated which retrieves a depth-resolved reflectance profile at the location of the probing beam and along an axial direction 440 of the fiber based device 406 (axis-scan). The resulting OCT data generated represents one-dimensional structural scattering information of the tissue being measured, such as inner or middle-ear tissue. Since the LCI signal in this case is fast, relative to small lateral movements between the ear speculum 404 and the ear 438, multiple axial-scans can be acquired rapidly, corresponding to a specific set of sampling data that can be analyzed by a computer using the core software unit 430 or reconstructed to produce a cross-section type of “image” associated with the continuous trace of these sampled regions. The resulting OCT data facilitates the detection of tissue structures including the eardrum 446, ossicles 448, and the presence of a bio film. In one embodiment, a traditional spectral-domain LCI system can be used as the core imaging unit 410 in order to generate an LCI signal and obtain OCT data.
All of the foregoing is known in the art, and has been described in the Boppart '934 patent.
It would be highly desirable, however, to provide physicians with direct access to the axis of motion of the eardrum (i.e., the axis of the ear canal), in a quantitative manner, and in relation to a known pressure in the ear canal. Additionally, it would also be highly desirable to provide micron-scale resolution for precise, quantitative measurements of eardrum motion under known pressure conditions. It would be still more useful that physicians retain access to 2D surface images to which they are accustomed. A device that could provide such functionality would be very beneficial.